The mission of St. Jude Children's Research Hospital is to find cures for children with catastrophic illnesses through research and treatment. The resources of the hospital have been focused on pediatric cancer throughout its 44 year history and the Cancer Center has been supported by a CCSG for 29 years. Through the support of the American Lebanese Syrian Associated Charities (ALSAC), a separate corporation whose only purpose is to raise money in support of St. Jude Children's Research Hospital, patients are accepted without regard to ability to pay. Public support of the hospital through ALSAC provides a strong foundation for our Cancer Center upon which extramurally funded research and CCSG support can be leveraged to their fullest potential. In the current application, six multidisciplinary research programs are described. The Molecular Oncology (MO) and Signal Transduction (ST) Programs focus on basic, discovery-oriented research. The Developmental Therapeutics for Solid Malignancies (DTSM), Hematologic Malignancies (HM), Neurobiology and Brain Tumor (NBT), and Cancer Prevention and Control (CPC) Programs emphasize the translation of laboratory or population science to clinical application. The latter program is new to this application and represents the culmination of a long-standing commitment to long-term follow-up of our patient population, a recent commitment to population sciences, and successful recruitment of a world-class scientist to lead efforts in this area. Research by the 139 members of the Cancer Center is supported by 12 Shared Resources and an outstanding clinical research infrastructure. During the previous funding period, a new Cancer Center Director was appointed and the overall structure of our Cancer Center and its leadership were enhanced by several organizational changes, including bringing the infrastructure supporting the expansive clinical trials efforts administratively under the Cancer Center's authority. Several Program leader changes and the successful recruitment of three new outstanding Department Chairs (Immunology, Chemical Biology, and Epidemiology/Cancer Control) during the last funding period significantly enhance the multidisciplinary science done by our Cancer Center Programs. St. Jude Cancer Center investigators had over 2000 cancer-related publications during the funding period, 20% of which represented intraprogrammatic interactions and 15% of which were inter-programmatic. Extramural support for cancer research done at St. Jude is currently over $50 million per year, $31 million of which is from the NCI/HHMI. St. Jude Children's Research Hospital recently went through a vigorous Strategic Planning process and made a strong and long-term commitment to remain focused on cancer research.